Novel Dissymmetric Ionizable Lipid-Assembled Lipid Nanoparticles for Delivery of Ferroptosis-Related siRNA in Diabetic Treatment
Small interfering RNA (siRNA) enables precise post-transcriptional gene silencing for refractory diseases, yet its clinical translation remains limited by the lack of safe and efficient delivery vectors. Inspired by the dissymmetric alkyl chain architecture of natural membrane phospholipids, we designed and synthesized 34 novel ionizable lipids with dissymmetric hydrophobic tails and formulated…
Researchers have developed innovative lipid nanoparticles (LNPs) designed to deliver ferroptosis-related siRNA for the treatment of diabetes. These LNPs are based on the unique dissymmetric alkyl chain structure found in natural membrane phospholipids, which allows for safer and more efficient delivery of gene silencing agents. The scientists synthesized 34 new ionizable lipids with these dissymmetric hydrophobic tails and tested them in both mouse models of type 2 diabetes.
Two lead LNPs, O14-LNP and H18a-LNP, emerged as the most effective, demonstrating superior endosomal escape, stronger gene silencing, and better safety profiles compared to previous LNP models. When these lead LNPs were used to deliver ferroptosis-related siRNA, they significantly improved glucose and lipid metabolism, restored pancreatic function, and reduced liver fat accumulation in diabetic mice.
This research not only provides a theoretical framework for designing new ionizable lipids but also confirms the potential of using siRNA targeting ferroptosis as a therapeutic strategy for diabetes, offering a promising delivery platform for this prevalent condition.
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